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Biomedical Imaging and Instrumentation

Biomedical Imaging and Instrumentation - Poster Session C

Poster G4 - Magnetic Resonance Imaging of Microfluidic Tumor Model Using Newly Designed Controlled Heating Apparatus (CHAMP-3)

Friday, October 25, 2024
10:00 AM - 11:00 AM EST
Location: Exhibit Hall E, F & G

Introduction:  Diagnosis of breast cancer using magnetic resonance imaging (MRI) often requires contrast agent-aided scans with gadolinium (Gd)-chelates. Gd-chelates lack specificity, resulting in false positive diagnoses that lead to unnecessary biopsies, further imaging, anxiety, and wasted medical dollars. Further, Gd-chelates can accumulate in the brain and bone, raising toxicity concerns. With the goal of developing a novel, accurate, and safe contrast agent for MRI, pH-sensitive Nano-Encapsulated Manganese Oxide (NEMO) particles have been at the forefront of our research. Typically, testing novel MRI contrast agents involves static 2D cell culture and in vivo MRI. 2D cell cultures lack dynamic flow; therefore, they often inaccurately predict in vivo outcomes. Long-term in vivo MRI studies have time-limiting factors such as anesthesia usage for murine models and temperature contraindications as well as high cost, long set-up time, and needed regulatory approval. 3D microfluidic tumor models (MTMs) bridge the gap between cell culture and animal models to create a platform that is cost-effective, reproducible, customizable, and high throughput; however, imaging microfluidic devices with MRI is difficult due to their small fluid volume and low sensitivity. The lack of a temperature-controlling system inside the MRI presents an additional challenge.

Materials and

Methods:  To enable long-term MRI of 3D MTMs, a three-part device called CHAMP-3 (controlled heating apparatus for microfluidics and portability) was designed. CHAMP-3 contains: (1) a 3D printed chip holder to secure the chip in the MRI and provide sufficient reference water to enhance MR signal, (2) a heated water perfusion apparatus to maintain MTM temperature at 37oC which promotes cell survival, and (3) a self-sustained power source for portability between the incubator and MRI room. First, temperature maintenance with CHAMP-3 was validated by perfusing RPMI media through the MTMs while the CHAMP-3 water bath was set to 66oC; a custom-made thermocouple data acquisition system measured the temperature of the fluid while an analog thermometer measured the surface temperature of the MTM. Next, T1-weighted MRI scans of 3D MTMs were acquired to estimate how the contrast-to-noise ratio changed after administering increasing Mn2+ concentrations (12.5µM to 200µM) in water and RPMI media through the chips. Higher Mn2+ concentrations up to 3200µM in water were also tested to capture the dynamic range of the manganese contrast within the chips. Repetition times (TRs) of 300 ms and 600 ms were used, and three trials were conducted for each solution. In addition, MRI was conducted on MTMs seeded with human T47D breast cancer cells pre and post administration of 100µM Mn2+ in RPMI.

Results, Conclusions, and Discussions: With CHAMP-3, the MTM surface reached 37oC after 25 min and was stable for 1 hour. Temperature of RPMI media flowing through the MTM stabilized at 34.2oC. For water solutions, CNR of MTMs increased with higher Mn2+ concentrations up to 200μM, plateaued until 400μM, and then decreased until 3200μM. CNR at 200µM Mn2+ in water was approximately 4.25-fold higher than DI water alone. At very high concentrations of Mn2+ in water (400µM to 3200µM), CNR significantly decreased due to the T2 shortening effects of Mn2+ outweighing its T1 shortening effects. For RPMI media solutions, CNR increased with higher Mn2+ concentrations up to 50μM and appeared to begin plateauing towards 200μM. The CNR at 200µM Mn2+ in RPMI was approximately 2.31-fold higher than RPMI alone. For all water and RPMI solutions, a TR of 600 ms resulted in slightly higher CNR than a TR of 300 ms. Preliminary MRI scans of T47D breast cancer cells seeded in MTMs indicated that the CNR increased post 100µM Mn2+ administration. For the first time, MRI of MTMs was performed at low field strength (1T) using conventional imaging equipment without microcoils. Results show that increased CNR in MTMs during MRI was observed with higher Mn2+ concentrations over the 200μM range. CHAMP-3 was also successful in providing a temperature-controlled environment to facilitate cell survival. Therefore, MRI of 3D MTMs shows promise of being a novel testing method for MRI contrast agents. Future experiments will assess longitudinal CNR change in MTMs seeded with breast cancer cells following NEMO particle administration.

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